Hexafluoro-t-butyl difluoromethyl ether as an inhalation anesthetic

ABSTRACT

Hexafluoro-t-butyl difluoromethyl ether of the formula   IS USEFUL AS AN INHALATION ANESTHETIC.

United States Patent [191 Croix [451 May 13, 1975 HEXAFLUORO-T-BUTYL DIFLUOROMETIIYL ETHER AS AN INHALATION ANESTHETIC Related U.S. Application Data [63] Continuation-impart of Ser. No. 326,481, Jan. 29, 1973, abandoned. which is a continuation of Ser No. 174,957, Aug. 8, I97], abandoned.

Louise S. Croix, Summit, NJ.

[52] U.S. CI. 424/342 [5 l] Int. Cl A6lk 27/00 [58] Field of Search 424/342 [56] References Cited FOREIGN PATENTS OR APPLICATIONS 735,828 9/1969 Belgium H 424/342 Primary ExaminerJerome D. Goldberg Attorney, Agent, or FirmR0ger M. Rathbun; Edmund W. Bopp; H. Hume Mathews [57] ABSTRACT Hexafluoro-t-butyl difluoromethyl ether of the for mula is useful as an inhalation anesthetic.

2 Claims, N0 Drawings 1 HEXAFLUORO-T-BUTYL DIFLUOROMETHYL ETI-IER AS AN INHALATION ANESTHETIC This application is a continuation-in-part of application Ser. No. 326,481 filed Jan. 29, 1973, now abandoned, which is a continuation of application Ser. No. 174,857 filed Aug. 8, 1971, now abandoned.

This invention relates to hexafluoro-t-butyl difluoromethyl ether and its use in producing anesthesia in anesthetic-susceptible mammals. The chemical formula of this ether is The compound of the present invention lends itself to effective use as an inhalant anesthetic in respirable mixtures containing life-supporting concentrations of oxygen, with or without other inhalation anesthetics, such as nitrous oxide. Administration of the compound may be by any of the well known techniques for administering general inhalation anesthetics, for example, by using the open drop, semi-closed, or closed systems.

The effective amount of the compound of this inven tion to be employed depends on the level of anesthesia to which the mammal is to be brought, the rate at which anesthesia is to be induced, and the length of time over which anesthesia is to be maintained. Minor volume percentages, generally about 4 or somewhat more volume percent of the compound in oxygen, can often be employed. The amount used should be sufficient to provide a significant anesthetic effect but so much as to produce unacceptable deleterious side effects. The amount of anesthetic to be used can be regulated, starting with a small amount of the ether and gradually increasing the amount until the desired plane of anesthesia is reached. By then monitoring the physical reactions of the mammal, as is the usual procedure, the duration and plane of anesthesia can be readily controlled.

The ether compound of this invention is also easily miscible with other organic liquids, including fats and oils, and has useful solvent properties, for example, as a solvent for fluorinated olefins and other fluorinated materials, such as fluoro waxes. The compound of this invention may be used to prepare pastes and dispersions of such materials useful for coatings and the like, and may be used as a degreasing agent. In the latter capacity, for example, the ether compound of this invention can be used as a solvent to remove grease or other oily substances from a metal surface that is to be painted.

The hexafluoro-t-butyl difluoromethyl ether of this invention can be made by reacting hexafluoro-tbutanol with fluorodichloromethane. As an example of a specific synthesis of the compound of this invention, into the liner of a 1 liter stainless steel autoclave was placed 182 g. (1 mole) of commercially obtained hexafluoro-t-butanol and 50 g. of methyl pyrrolidone as a solvent. The sealed autoclave was stirred while 86.5 g. (1 mole) of commercially obtained fluorodichlorornethane was added as a liquid (74 ml.) through a pressure burette. A 50% solution of NaOH (243 g, 3 moles) followed at such a rate as to maintain the reaction temperature at 30-40C. with outside cooling. After an additional 1 hour of stirring at 35C., the autoclave was opened and the contents distilled. From the first fraction (51 g., bp: 62-3C.) was separated by preparative chromatography 26.7 g. of (CF (CH )C-O-CHF Calculated for C H F O: C, 25.9; H, 1.7; F, 65.5 Found: C, 26.1; H, 1.8; F, 65.4.

This normally liquid compound has a boiling point of C., a specific gravity of 1.50, a vapor pressure at 25C. of mm. Hg, and a refractive index (n,, of 1.2847. The compound is odorless and borderline as regards flammability.

In order to determine the potency of the aliphatic ether of the present invention as an inhalation anesthetic in combination with oxygen, tests were carried out on mice. The sample tested was at least 99.5% pure as determined by vapor phase chromatography. In the tests, the ether compound is administered to test mice by a standard procedure in which a measured quantity of the agent is placed in a laboratory jar and allowed to completely vaporize so as to give a calculated vapor concentration. The test mice are then quickly placed in the jar and observed. Anesthesia is determined by ob serving the righting reflex of the mice. Recovery time is measured beginning when the mice are transferred from the test jar to room air and ending when the mice are observed to be able to walk.

In such tests, the hexafluoro-t-butyl difluoromethyl ether, when used at a vapor concentration of 2.5%, induced a very light anesthesia in 1 minute, 37 seconds. There was moving throughout maintenance of the anesthesia, and recovery therefrom required 15 seconds. At 4.0%, the induction time was 59 seconds and the recovery time was 39 seconds. Again, there was moving throughout maintenance. When used at a vapor concentration of 8.0%, the induction time was shortened to 19 seconds and the recovery period lengthened to 2 minutes, 13 seconds. Maintenance was accompanied by respiratory depression and, once again, by moving of the subjects, thus indicating that the use of larger concentrations might be desirable in some circumstances.

Since volatile general anesthetics today are generally administered in a closed system involving recycling the exhaled gases for conservation of the relatively expensive agents and protection of operating room personnel, it is required that commercially useful volatile anesthetics intrinsically have good soda-lime stability as does the compound of the present invention. The compound of the present invention, (CF C(CH )OCHF was subjected to soda-lime for a period of 18 hours to determine its soda-lime stability. The soda-lime was analyzed before and after the test for fluoride ion content. One hundred eighty-eight parts per million fluoride was found to be present before the test and 214 parts per million after the test. These results establish that the tested compound exhibited negligible ion loss and excellent soda-lime stability.

While there has been described what are at present considered to be preferred embodiments of the invention, it will be understood that various modifications may be made therein which are within the true spirit and scope of the invention.

I claim:

1. An inhalant anesthetic composition comprising hexafluoro-t-butyl difluoromethyl ether of the formula:

and oxygen in suitable proportions for use us an anesthetic.

2. A method of anesthctizing an anestheticsusceptihle mammal which Comprises administering to the mammal an anesthctically effective amount of hex afluorp-t-butyl difluoromethyl ether of the formula:

supporting amounts of oxygen. 

1. An inhalant anesthetic composition comprising hexafluoro-t-butyl difluoromethyl ether of the formula:
 2. A METHOD OF ANESTHETIZING AN ANESTHETIC-SUSCEPTIBLE MAMMAL WHICH COMPRISES ADMINISTERING TO THE MAMMAL AN ANESTHETICALLY EFFECTIVE AMOUNT OF HEXAFLUORO-T-BUTYL DIFLUOROMETHYL ETHER OF THE FORMULA: 